In recent years genes for several rare, monogenic epilepsy syndromes have been discovered, but identifying genes involved in the more common, complex human epilepsies has been more difficult. Linkage studies performed to date have focused on homogeneous families with affected status based on syndromic classification. Less is known about how to analyze the overlap between epilepsy syndromes or how to address the phenotypic heterogeneity seen within an individual family. Evidence suggests that epilepsy involves susceptibility genes that influence overall risk for recurrent seizures, as well as modifier genes that influence the phenotypic features of epilepsy, such as seizure type, age of onset, seizure frequency and seizure severity. Understanding the inheritance of individual components of the epilepsy phenotype is a key step to understanding heterogeneity in the human epilepsies, and to identifying novel disease genes in the presence of such heterogeneity. The objective of this Mentored Patient-Oriented Research Career Development Award is to use novel methods of linkage analysis and epilepsy phenotyping to overcome genetic heterogeneity in gene mapping efforts. The parallel objective is to develop the applicant into an independent clinical investigator in the genetic epidemiology of epilepsy through experience in the design, data collection and data analysis of family-based genetic studies. The applicant will pursue the following Specific Aims: 1) To determine the familiarity of phenotypic features of epilepsy, 2) To evaluate electrophysiological traits as markers of epilepsy, and 3) To identify genetic loci underlying phenotypic features of epilepsy. The applicant, who is trained as a clinical neurologist with specialty training in epilepsy and clinical neurophysiology, will pursue further training in genetic epidemiology and statistical genetics as part of the career development plan. The work proposed will be significant in that it will introduce new tools in the search for epilepsy disease loci in the common, complex epilepsies. Drs. Elston, Wang, Luders, Burgess, lyengar and Ottman will provide mentorship and guidance of a multidisciplinary nature encompassing clinical epilepsy, clinical neurophysiology, biomedical engineering, genetic epidemiology, statistical genetics and molecular genetics.